Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough

A Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03282591

Enrollment

185

Registered

2017-09-14

Start date

2017-10-03

Completion date

2018-09-06

Last updated

2021-05-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Refractory Chronic Cough

Brief summary

Study of the efficacy, safety, and tolerability of serlopitant for the treatment of refractory chronic cough

Interventions

DRUG5 mg Serlopitant Tablets

Serlopitant Tablets

DRUGMatching Placebo Tablets

Placebo Tablets

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Female and males between 18 and 80 years of age * Have a diagnosis of treatment refractory chronic cough or unexplained cough for at least one year * Chest radiograph or computed tomography (CT) Thorax within the last 5 years not demonstrating any abnormality considered to be significantly contributing to the chronic cough * At Screening have a score of ≥ 40mm on the Cough Severity VAS * At Baseline (Day 0) have a score of ≥ 40mm on the Cough Severity VAS * All female subjects who are of childbearing potential must practice highly effective contraception (i.e., pregnancy prevention method with a failure rate of \< 1% per year) from the time of the initial screening visit until 4 weeks after last dose of study drug. Please refer to the protocol for acceptable methods of contraception

Exclusion criteria

* Prior treatment with serlopitant or other NK1-R antagonist * Presence of any medical condition or disability that could interfere with study * History of hypersensitivity to serlopitant or any of its components * Currently pregnant or male partner of pregnant female * Females of childbearing potential who are unable or unwilling to use adequate contraception or who are breast feeding * Current smoker or individuals who have given up smoking within the past 12 months * FEV1/FVC \< 60% * Body mass index (BMI) \<18 kg/m2 or ≥ 40 kg/m2 at Screening * History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0) * History of cystic fibrosis * History of opioid use within 1 week of the Baseline Visit (Day 0) * Requiring concomitant therapy with prohibited medications * Treatment with biologic therapies within 8 weeks or 5 half-lives prior to the Baseline Visit (Day 0), whichever is longer * Treatment with strong CYP3A4 inhibitors within 4 weeks prior to the Baseline Visit (Day 0) * Treatment with any investigational therapy within 4 weeks (investigational biologic therapies within 8 weeks) prior to the Baseline Visit (Day 0) * Serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2x the upper limit of normal (ULN) during screening * Positive test for any drug of abuse * History of malignancy within 5 years prior to the Baseline Visit (Day 0), with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin * Any known psychiatric diagnosis meeting DSM-5 criteria which may confound the assessment of serlopitant safety or efficacy, or interfere with the subject's ability to comply with protocol-mandated activities, within 3 years prior to randomization. Examples of such DSM-5 diagnoses include but are not limited to major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder. * Known active hepatitis infection * Known history of human immunodeficiency virus (HIV) infection

Design outcomes

Primary

Measure	Time frame	Description
Change in 24-hour Objective Cough Frequency (Log Normalized Percent Change Relative to Placebo)	from Baseline to Day 84	Change in 24-hour objective cough frequency is total number of cough events during the monitoring period (24-hour interval)/24 (Total duration (in hours) for the monitoring period) which is captured through sound recordings by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).

Secondary

Measure	Time frame	Description
Change in Awake Objective Cough Frequency	from Baseline to Day 84	Awake cough frequency = (total number of cough events during the monitoring period (24-hour interval) the subject is awake)/(Total duration (in hours) for the monitoring period the subject is awake) which is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).
Percentage of Participants With ≥ 30% Reduction in 24-hour Objective Cough Frequency	from Baseline to Day 84	The percentage of participants with ≥ 30% of reduction from baseline in 24-hour cough frequency is the number of participants with ≤-30% change in 24-hour cough frequency divided by the total number of participants with available data. This data is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).
Percentage of Participants With ≥30% Reduction in Awake Objective Cough Frequency	from Baseline to Day 84	The percentage of participants with ≥ 30% of reduction from baseline in the awake cough frequency is the number of participants with ≤30% change in awake cough frequency divided by the total number of participants with available data. This data is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).
Change From Baseline in Cough Severity Visual Analog Scale (VAS)	from Baseline to Day 84	Visual Analog Scale (VAS) 101-point scale ranging from 0 (no cough) to 100 (worst cough). A higher score corresponds to higher cough severity.

Countries

United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Serlopitant 5 mg Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a tablet taken once daily for 84 days.	88
Placebo Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a tablet taken once daily for 84 days.	88
Total	176

Baseline characteristics

Characteristic	Total	Serlopitant 5 mg	Placebo
Age, Continuous	65 years	62.7 years STANDARD_DEVIATION 11.21	62.6 years STANDARD_DEVIATION 10.09
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	5 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	170 Participants	83 Participants	87 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	7 Participants	3 Participants	4 Participants
Race (NIH/OMB) More than one race	NA Participants	NA Participants	NA Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	166 Participants	83 Participants	83 Participants
Region of Enrollment United Kingdom	39 participants	19 participants	20 participants
Region of Enrollment United States	137 participants	69 participants	68 participants
Sex: Female, Male Female	135 Participants	68 Participants	67 Participants
Sex: Female, Male Male	41 Participants	20 Participants	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 92	0 / 92
other Total, other adverse events	43 / 92	28 / 92
serious Total, serious adverse events	3 / 92	3 / 92

Outcome results

Primary

Change in 24-hour Objective Cough Frequency (Log Normalized Percent Change Relative to Placebo)

Change in 24-hour objective cough frequency is total number of cough events during the monitoring period (24-hour interval)/24 (Total duration (in hours) for the monitoring period) which is captured through sound recordings by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd).